Diets containing more than 15 % refined crystalline fructose have been shown to increase fasting and postprandial triglyceride levels. This rise in plasma triglyceride levels may play a role in insulin resistance, and raised triglyceride levels are in turn a risk factor for cardiovascular disease. Unlike glucose which can be metabolised by skeletal muscle, ingested fructose can only be metabolised by the liver. In the liver fructose is broken down to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which are converted to glycerol and acetyl-CoA respectively. Glycerol and acetyl-CoA are used in the synthesis of fatty acids in a process called de novo lipogenesis. The newly created lipids are packaged in very low density lipoproteins (VLDL) and then enter circulation, thus increasing circulating triglycerides. These VLDL are 85 % triglycerides and there destination is peripheral tissues. If their triglycerides are lipolysed to fatty acids and deposited in skeletal muscle, they thought to contribute to insulin resistance.
To investigate the mechanisms involved in fructose-induced hypertriglyceridaemia, researchers1 fed 14 subjects a test meal of either 0.75 grams per kg of body weight of refined glucose or refined fructose following an overnight fast. The meal was prepared with radiolabeled palmitate and either radiolabelled D-fructose or D-glucose in order to trace the fate of the sugars and fatty acid in the subjects via blood samples that were taken before and after the meals. Fructose consumption resulted in a significantly lower level of insulin release and radiolabeled palmitate in non-esterified fatty acids. However, levels of VLDL-triglycerides were significantly higher after the fructose meal. The production of radiolabeled carbon dioxide was higher after fructose than glucose, indicating significantly more fructose than glucose was oxidised. Higher respiratory exchange ratios were observed after the fructose meal indicating that higher carbohydrate and lower fatty acid oxidation rates were taking place.
Newly synthesised fatty acids and glycerol from radiolabeled fructose made up 0.4 % and 38 % of VLDL-triglycerides at 240 min, respectively. In contrast, newly synthesised fatty acids and glycerol from glucose were not present in VLDL-triglycerides. This suggests that the fructose contribution to the glycerol components of the triglycerides is more than that of the fatty acid component. It also suggests that fructose has greater lipogenic effects than glucose. Only small quantities of fructose was converted to fatty acids and triglyceride-glycerol at 240 min (0.05 % and 0.15 % respectively). Over the course of the experiment the authors concluded that < 1% of the fructose would have been converted to VLDL. The authors suggested that the contribution of fructose to de novo lipogenesis might be small, but fructose may increase VDLD-triglyceride levels because it increases the partitioning of fatty acids towards esterification. Either way, fructose increases fatty acid production through the de novo lipogenesis pathway.
Dr Robert Barrington’s Comments: Sucrose and high fructose corn syrup consumption in the United States has increased from 64 grams per day in 1970 to 81 grams per day in 1997. These intakes equate closely to the amount of fructose ingested in this study making it relevant to the real World. Although fructose does contribute directly to increased flux through the de novo lipogenesis pathway, it may further increase circulating triglyceride levels by reducing the removal of triglycerides from circulation through a reduced activation of adipose tissue lipoprotein lipase. This results because lipoprotein lipase activity is upregulated by insulin, but fructose does not cause insulin release. In addition fructose may increase liver concentrations of malonyl-CoA, an intermediate in the pathway of de novo lipogenesis, which in turn inhibits carnitine-palmitoyl transferase-1, the enzyme involved in the transport of long-chain fatty acids into the mitochondria. The result is that fatty acids are channelled toward esterification.
RdB
